関: 1,25-dihydroxycholecalciferol、1,25-dihydroxyvitamin D3、calcitriol

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/20 17:48:00」(JST)

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Calcitriol (INN) /kælˈsɪtri.ɒl/, also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D₃, is the hormonally active form of vitamin D with three hydroxyl groups (abbreviated 1,25-(OH)₂D₃ or simply 1,25(OH)₂D),^[1] It was first identified by Michael F. Holick in work published in 1971.^[2] Calcitriol increases the level of calcium (Ca²⁺) in the blood by (1) increasing the uptake of calcium from the gut into the blood, and (2) possibly increasing the release of calcium into the blood from bone.^[3]

Nomenclature[edit]

Calcitriol usually refers specifically to 1,25-dihydroxycholecalciferol, but may also sometimes include 24,25-dihydroxycholecalciferol (when specified). 24,25-dihydroxycholecalciferol is the deactivated form of vitamin D.^{[citation needed]}

Because cholecalciferol already has one hydroxyl group, only two are further specified in the nomenclature.

Pharmaceutical trade names[edit]

Calcitriol is marketed under various trade names including Rocaltrol (Roche), Calcijex (Abbott), Decostriol (Mibe, Jesalis) and Vectical (Galderma).

Function[edit]

Calcitriol increases blood calcium levels ( [Ca²⁺] ) by promoting absorption of dietary calcium from the gastrointestinal tract and increasing renal tubular reabsorption of calcium thus reducing the loss of calcium in the urine. Calcitriol also stimulates release of calcium from bone by its action on the specific type of bone cells referred to as osteoblasts, causing them to release RANKL, which in turn activates osteoclasts.^[4]

Calcitriol acts in concert with parathyroid hormone (PTH) in all three of these roles. For instance, PTH also indirectly stimulates osteoclasts. However, the main effect of PTH is to increase the rate at which the kidneys excrete inorganic phosphate (P_i), the counterion of Ca²⁺. The resulting decrease in serum phosphate causes Ca₅(PO₄)₃OH to dissolve out of bone thus increasing serum calcium. PTH also stimulates the production of calcitriol (see below).^[3]

Many of the effects of calcitriol are mediated by its interaction with the calcitriol receptor, also called the vitamin D receptor or VDR. For instance, the unbound inactive form of the calcitriol receptor in intestinal epithelial cells resides in the cytoplasm. When calcitriol binds to the receptor, the ligand-receptor complex translocates to the cell nucleus, where it acts as a transcription factor promoting the expression of a gene encoding a calcium binding protein. The levels of the calcium binding protein increase enabling the cells to actively transport more calcium (Ca²⁺) from the intestine across the intestinal mucosa into the blood.^[3]

The maintenance of electroneutrality requires that the transport of Ca²⁺ ions catalyzed by the intestinal epithelial cells be accompanied by counterions, primarily inorganic phosphate. Thus calcitriol also stimulates the intestinal absorption of phosphate.^[3]

The observation that calcitriol stimulates the release of calcium from bone seems contradictory, given that sufficient levels of serum calcitriol generally prevent overall loss of calcium from bone. It is believed that the increased levels of serum calcium resulting from calcitriol-stimulated intestinal uptake causes bone to take up more calcium than it loses by hormonal stimulation of osteoclasts.^[3] Only when there are conditions, such as dietary calcium deficiency or defects in intestinal transport, which result in a reduction of serum calcium does an overall loss of calcium from bone occur.

Calcitriol also inhibits the release of calcitonin,^{[citation needed]} a hormone which reduces blood calcium primarily by inhibiting calcium release from bone.^[3] (The effect of calcitonin on renal excretion is disputed.)^[5]

Biosynthesis and its regulation[edit]

Calcitriol is produced in the cells of the proximal tubule of the nephron in the kidneys by the action of 25-hydroxyvitamin D₃ 1-alpha-hydroxylase, a mitochondrial oxygenase and an enzyme which catalyzes the hydroxylation of 25-hydroxycholecalciferol (calcifediol). The activity of the enzyme is stimulated by PTH. The reaction is an important control point in Ca²⁺ homeostasis.^[3]

The production of calcitriol is also increased by prolactin, a hormone which stimulates lactogenesis (the formation of milk in mammary glands), a process which requires large amounts of calcium. It is decreased by high levels of serum phosphate and by an increase in the production of the hormone FGF-23 by osteocyte cells in bone.^{[citation needed]}

Metabolism[edit]

Calcitriol becomes calcitroic acid through the action of 24-hydroxylase. Calcitroic acid is excreted in the urine.

Medical use[edit]

Calcitriol is prescribed for:^[6]

Treatment of hypocalcaemia – hypoparathyroidism, osteomalacia (adults), rickets (infants, children), renal osteodystrophy, chronic renal dialysis
Treatment of osteoporosis
Prevention of corticosteroid-induced osteoporosis

Calcitriol is also sometimes used topically in the treatment of psoriasis, however the evidence to support its efficacy is not well established.^[7] The vitamin D analogue calcipotriol is more commonly used for psoriasis. Research on the noncalcemic actions of calcitriol and other VDR-ligand analogs and their possible therapeutic applications has been reviewed.^[8]

Calcitriol is also administered orally for the treatment of psoriasis^[9] and psoriatic arthritis.^[10]

Adverse effects[edit]

The main adverse drug reaction associated with calcitriol therapy is hypercalcaemia – early symptoms include: nausea, vomiting, constipation, anorexia, apathy, headache, thirst, sweating, and/or polyuria. Compared to other vitamin D compounds in clinical use (cholecalciferol, ergocalciferol), calcitriol has a higher risk of inducing hypercalcaemia. However, such episodes may be shorter and easier to treat due to its relatively short half-life.^[6]

Interactive pathway map[edit]

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Vitamin D Synthesis Pathway edit

^ The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

Additional images[edit]

Calcitriol synthesis

References[edit]

^ "Nomenclature of Vitamin D. Recommendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.
^ Holick, MF; Schnoes, HK; Deluca, HF; Suda, T; Cousins, RJ (1971). "Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine". Biochemistry 10 (14): 2799–804. doi:10.1021/bi00790a023. PMID 4326883.
^ ^a ^b ^c ^d ^e ^f ^g Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons. ISBN 0-471-25090-2.
^ Bringhurst, F. R; Demay, Marie B.; Krane, Stephen M.; Kronenberg, Henry M. "Bone and Mineral Metabolism in Health and Disease", chapter 346 in Fauci, Anthony S.; Braunwald, E.; Kasper, D. L.; Hauser, S. L.; Longo D. L.; Jameson, J. L.; Loscalzo, J. (2008). Harrison's Principles of Internal Medicine, 17th edition. New York: McGraw-Hill. ISBN 978-0-07-159991-7. Available online at AccessMedicine.com, purchase required.
^ Carney SL (1997). "Calcitonin and human renal calcium and electrolyte transport". Miner Electrolyte Metab 23 (1): 43–7. PMID 9058369.
^ ^a ^b Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3
^ Calcitriol. In: Klasco RK, editor. Drugdex system. vol 128. Greenwood Village (CO): Thomson Micromedex; 2006.
^ Nagpal, S.; Na, S.; Rathnachalam, R. (2005). "Noncalcemic Actions of Vitamin D Receptor Ligands". Endocrine Reviews 26 (5): 662–687. doi:10.1210/er.2004-0002. PMID 15798098. edit.
^ Smith, E. L.; Pincus, S. H.; Donovan, L.; Holick, M. F. (1988). "A novel approach for the evaluation and treatment of psoriasis". Journal of the American Academy of Dermatology 19 (3): 516–528. doi:10.1016/S0190-9622(88)70207-8. PMID 2459166. edit
^ Huckins, D.; Felson, D. T.; Holick, M. (1990). "Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: A pilot study". Arthritis & Rheumatism 33 (11): 1723. doi:10.1002/art.1780331117. edit

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 慢性腎臓病に伴う骨・ミネラル代謝異常（CKD-MBD）の概要 overview of chronic kidney disease mineral bone disease ckd mbd
2. 乾癬の治療 treatment of psoriasis
3. ビタミンD欠乏症の原因および抵抗性 causes of vitamin d deficiency and resistance
4. 副甲状腺ホルモンの分泌および作用 parathyroid hormone secretion and action
5. 副甲状腺機能低下症 hypoparathyroidism

English Journal

Optimal vitamin D, calcitriol, and vitamin D analog replacement in chronic kidney disease: to D or not to D: that is the question.

Moorthi RN, Kandula P, Moe SM.SourceaDivision of Nephrology, Indiana University School of Medicine, USA bRoudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA.
Current opinion in nephrology and hypertension.Curr Opin Nephrol Hypertens.2011 Jul;20(4):354-9.
PURPOSE OF REVIEW: Patients with chronic kidney disease (CKD) are often insufficient in 25(OH) vitamin D and are almost uniformly deficient in 1,25(OH)2 vitamin D, because of decreased renal hydroxylation resulting from hyperphosphatemia and elevated fibroblast growth factor-23 (FGF-23) levels. Thes
PMID 21654391

Vitamin d deficiency, inflammation, and albuminuria in chronic kidney disease: complex interactions.

Isakova T, Gutierrez OM, Patel NM, Andress DL, Wolf M, Levin A.SourceDivision of Nephrology and Hypertension, Leonard M. Miller School of Medicine, University of Miami, Miami, Florida.
Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation.J Ren Nutr.2011 Jul;21(4):295-302. Epub 2010 Sep 3.
OBJECTIVE: Vitamin D may promote cardiovascular health in general population and in chronic kidney disease (CKD) through inhibition of the renin-angiotensin system and anti-inflammatory effects. Although proteinuria is a marker of kidney and cardiovascular disease, few studies have examined vitamin
PMID 20817560

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★リンクテーブル★

リンク元	「カルシトリオール」「1,25-dihydroxyvitamin D3」

「カルシトリオール」

Calcitriol
Systematic (IUPAC) name
	(1R,3S)-5-[2-[(1R,3aR,7aS)-1-[(2R)-6-hydroxy-6-methyl-heptan-2-yl]-7a-methyl-2,3,3a,5,6,7-hexahydro-1H- inden-4-ylidene]ethylidene]-4-methylidene-cyclohexane-1,3-diol
Clinical data
Trade names	Rocaltrol, Calcijex, Decostriol
MedlinePlus	a682335
Pregnancy cat.	B3 (AU) C (US)
Legal status	Prescription Only (S4) (AU) ℞-only (CA) POM (UK) ℞-only (US)
Routes	Oral, IV, topical
Pharmacokinetic data
Protein binding	99.9%
Metabolism	Renal
Half-life	5–8 hours (adults), 27 hours (children)
Excretion	Faeces (50%), urine (16%)
Identifiers
CAS number	32222-06-3
ATC code	A11CC04 D05AX03
PubChem	CID 5280453
IUPHAR ligand	2779
DrugBank	DB00136
ChemSpider	4444108
UNII	FXC9231JVH
ChEBI	CHEBI:17823
ChEMBL	CHEMBL846
Chemical data
Formula	C27H44O3
Mol. mass	416.64 g/mol
	SMILES C[C@H](CCCC(C)(C)O)[C@H]1CC[C@@H]\2[C@@]1(CCC/C2=C\C=C/3\C[C@H](C[C@@H](C3=C)O)O)C;
	InChI InChI=1S/C27H44O3/c1-18(8-6-14-26(3,4)30)23-12-13-24-20(9-7-15-27(23,24)5)10-11-21-16-22(28)17-25(29)19(21)2/h10-11,18,22-25,28-30H,2,6-9,12-17H2,1,3-5H3/b20-10+,21-11-/t18-,22-,23-,24+,25+,27-/m1/s1 ; Key:GMRQFYUYWCNGIN-NKMMMXOESA-N ;
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英: calcitriol, 1α,25-(OH)2-D3
同: 1α,25-ジヒドロキシコレカルシフェロール 1α,25-dihydroxycholecalciferol; 1α,25-ジヒドロキシビタミンD3 1α,25-dihydroxyvitamin D3
商: Calcijex; オタノール、カルシオロール、カルシタロール、カルデミン、カルトール、カルミサール、チコカロール、トルシトリン、ヒポテリオール、フルスタン、ホーネル、リストール、ロカルシトール、ロカルトロール Rocaltrol
関: 1,25-ジヒドロキシビタミンD3、1,25-ジヒドロキシコレカルシフェロール。ビタミンＡ及びＤ剤

「1,25-dihydroxyvitamin D3」

　　[★]

関: 1,25-dihydroxycholecalciferol、calcitriol、Rocaltrol

[WikiPathways-11] The interactive pathway map can be edited at WikiPathways: "VitaminDSynthesis_WP1531".

[1] "Nomenclature of Vitamin D. Recommendations 1981. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN)" reproduced at the Queen Mary, University of London website. Retrieved 21 March 2010.

[2] Holick, MF; Schnoes, HK; Deluca, HF; Suda, T; Cousins, RJ (1971). "Isolation and identification of 1,25-dihydroxycholecalciferol. A metabolite of vitamin D active in intestine". Biochemistry 10 (14): 2799–804. doi:10.1021/bi00790a023. PMID 4326883.

[Voet-3] ^ ^a ^b ^c ^d ^e ^f ^g Voet, Donald; Voet, Judith G. (2004). Biochemistry. Volume one. Biomolecules, mechanisms of enzyme action, and metabolism, 3rd edition, pp. 663–664. New York: John Wiley & Sons. ISBN 0-471-25090-2.

[4] Bringhurst, F. R; Demay, Marie B.; Krane, Stephen M.; Kronenberg, Henry M. "Bone and Mineral Metabolism in Health and Disease", chapter 346 in Fauci, Anthony S.; Braunwald, E.; Kasper, D. L.; Hauser, S. L.; Longo D. L.; Jameson, J. L.; Loscalzo, J. (2008). Harrison's Principles of Internal Medicine, 17th edition. New York: McGraw-Hill. ISBN 978-0-07-159991-7. Available online at AccessMedicine.com, purchase required.

[pmid9058369-5] Carney SL (1997). "Calcitonin and human renal calcium and electrolyte transport". Miner Electrolyte Metab 23 (1): 43–7. PMID 9058369.

[AMH2006-6] Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006. ISBN 0-9757919-2-3

[MicromedexDrugdex-7] Calcitriol. In: Klasco RK, editor. Drugdex system. vol 128. Greenwood Village (CO): Thomson Micromedex; 2006.

[8] Nagpal, S.; Na, S.; Rathnachalam, R. (2005). "Noncalcemic Actions of Vitamin D Receptor Ligands". Endocrine Reviews 26 (5): 662–687. doi:10.1210/er.2004-0002. PMID 15798098. edit.

[9] Smith, E. L.; Pincus, S. H.; Donovan, L.; Holick, M. F. (1988). "A novel approach for the evaluation and treatment of psoriasis". Journal of the American Academy of Dermatology 19 (3): 516–528. doi:10.1016/S0190-9622(88)70207-8. PMID 2459166. edit

[10] Huckins, D.; Felson, D. T.; Holick, M. (1990). "Treatment of psoriatic arthritis with oral 1,25-dihydroxyvitamin D3: A pilot study". Arthritis & Rheumatism 33 (11): 1723. doi:10.1002/art.1780331117. edit

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Rocaltrol